Otton R, Mendonça J R, Curi R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900 Butantan, São Paulo, Brazil.
J Endocrinol. 2002 Jul;174(1):55-61. doi: 10.1677/joe.0.1740055.
An enhanced susceptibility to infections is well known to occur in a poorly controlled diabetic state. Since glucose and glutamine are essential for lymphocyte function, we investigated whether their metabolism is changed in lymphocytes obtained from mesenteric lymph nodes of alloxan-induced diabetic rats (40 mg/kg body weight). The activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase and phosphate-dependent glutaminase were determined. Decarboxylation of metabolites [U-14C]-, [1-14C]- and [6-14C]-glucose, [1-14C]- and [2-14C]-pyruvic acid, [U-14C]-palmitic acid and [U-14C]-glutamine was evaluated in incubated lymphocytes isolated from mesenteric lymph nodes. The measurements were carried out in cells following three experimental protocols: (1) lymphocytes freshly obtained from control and alloxan-induced diabetic rats, (2) lymphocytes from insulin-treated (2 U/rat per day) diabetic rats and (3) lymphocytes obtained from control and diabetic rats and cultured in the presence of insulin (1 mU/ml) for 6 h. The activities of hexokinase, G6PDH and citrate synthase were decreased by the diabetic state, whereas that of phosphofructokinase was raised. Decarboxylation of [U-14C]- and [6-14C]-glucose, [1-14C]- and [2-14C]-pyruvate and [U-14C]-glutamine were also decreased in lymphocytes from diabetic rats, whereas [U-14C]-palmitic acid decarboxylation was increased. Insulin administration in vivo or added to the culture medium reversed the changes observed in freshly obtained lymphocytes. Alloxan-induced diabetes did change lymphocyte metabolism and this may be an important mechanism leading to impairment of lymphocyte function.
众所周知，在糖尿病控制不佳的状态下，感染易感性会增强。由于葡萄糖和谷氨酰胺对淋巴细胞功能至关重要，我们研究了从四氧嘧啶诱导的糖尿病大鼠（40毫克/千克体重）肠系膜淋巴结获取的淋巴细胞中，它们的代谢是否发生了变化。测定了己糖激酶、磷酸果糖激酶、葡萄糖-6-磷酸脱氢酶（G6PDH）、柠檬酸合酶和磷酸依赖性谷氨酰胺酶的活性。评估了[U-14C]-、[1-14C]-和[6-14C]-葡萄糖、[1-14C]-和[2-14C]-丙酮酸、[U-14C]-棕榈酸和[U-14C]-谷氨酰胺在从肠系膜淋巴结分离的培养淋巴细胞中的脱羧情况。测量是按照三种实验方案在细胞中进行的：（1）从对照和四氧嘧啶诱导的糖尿病大鼠新鲜获取的淋巴细胞，（2）来自胰岛素治疗（每天2单位/大鼠）的糖尿病大鼠的淋巴细胞，以及（3）从对照和糖尿病大鼠获取并在胰岛素（1毫单位/毫升）存在下培养6小时的淋巴细胞。糖尿病状态使己糖激酶、G6PDH和柠檬酸合酶的活性降低，而磷酸果糖激酶的活性升高。糖尿病大鼠淋巴细胞中[U-14C]-和[6-14C]-葡萄糖、[1-14C]-和[2-14C]-丙酮酸以及[U-14C]-谷氨酰胺的脱羧也减少，而[U-14C]-棕榈酸脱羧增加。体内给予胰岛素或添加到培养基中可逆转在新鲜获取的淋巴细胞中观察到的变化。四氧嘧啶诱导的糖尿病确实改变了淋巴细胞代谢，这可能是导致淋巴细胞功能受损的重要机制。
